Cancer Genetics and Epigenetics 2024, Vol.12, No.6, 329-345 http://medscipublisher.com/index.php/cge 340 Targeting the epigenetic regulation of ncRNAs in ovarian cancer offers significant therapeutic potential. Current therapies involving DNMT and HDAC inhibitors have shown promise, and emerging approaches such as synthetic ncRNA mimics and CRISPR-based epigenetic editing hold great potential for improving treatment outcomes. However, challenges related to specificity, delivery, and resistance need to be addressed to fully realize the benefits of these innovative therapies. Continued research and development in this field are essential for advancing the treatment of ovarian cancer and improving patient outcomes. 9 Challenges and Future Directions 9.1 Research gaps: lack of mechanistic understanding of ncRNA-epigenetic interactions Despite significant advancements in the field of non-coding RNAs (ncRNAs) and their role in cancer, there remains a substantial gap in our mechanistic understanding of how ncRNAs interact with epigenetic machinery. Non-coding RNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been shown to play crucial roles in regulating gene expression and contributing to tumorigenesis (Anastasiadou et al., 2017; Kumar et al., 2020; Khan et al., 2021). However, the precise molecular mechanisms through which these ncRNAs influence epigenetic modifications, such as DNA methylation and histone modification, are not fully elucidated. For instance, while it is known that lncRNAs can interact with chromatin-modifying complexes to regulate gene expression, the specific pathways and interactions involved are still being uncovered (Forrest and Khalil, 2017; Zhang et al., 2020). Similarly, miRNAs are known to target mRNA for degradation or translational repression, but their role in modulating epigenetic states remains less clear (Wei et al., 2017; Kumar et al., 2020). The complexity of these interactions is further compounded by the dynamic nature of the epigenome, which can vary significantly between different types of cancer and even between different stages of tumor development (Ferreira and Esteller, 2018; Pathania, 2023). 9.2 Technological advances: need for more precise techniques to study ncRNA functions The study of ncRNAs and their epigenetic roles in cancer has been greatly facilitated by advances in high-throughput sequencing and bioinformatics tools. However, there is a pressing need for more precise and sophisticated techniques to dissect the complex regulatory networks involving ncRNAs. Current methods, such as RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq), provide valuable insights but often lack the resolution needed to fully understand the spatial and temporal dynamics of ncRNA-epigenetic interactions (Slack and Chinnaiyan, 2019; Kumar et al., 2020). Emerging technologies, such as single-cell RNA sequencing (scRNA-seq) and CRISPR-based epigenome editing, hold promise for addressing these challenges. Single-cell RNA sequencing allows for the analysis of gene expression at the individual cell level, providing a more detailed view of the heterogeneity within tumors (Anastasiadou et al., 2017; Saadi et al., 2022). CRISPR-based tools, on the other hand, enable precise manipulation of specific genomic loci, allowing researchers to directly test the functional consequences of ncRNA-epigenetic interactions (Forrest and Khalil, 2017; Zhang et al., 2020). Additionally, advanced imaging techniques, such as super-resolution microscopy, can help visualize the spatial organization of ncRNAs and their associated epigenetic marks within the nucleus (Pathania, 2023). 9.3 Potential for personalized medicine: exploring ncrnas as biomarkers and therapeutic targets The potential of ncRNAs as biomarkers and therapeutic targets in ovarian cancer is immense. Given their involvement in key regulatory processes, ncRNAs can serve as sensitive and specific biomarkers for early diagnosis, prognosis, and monitoring of treatment response (Ferreira and Esteller, 2018; Slack and Chinnaiyan, 2019; Kumar et al., 2020). For example, the aberrant expression of certain miRNAs and lncRNAs has been linked to poor prognosis and resistance to chemotherapy in ovarian cancer patients (Wei et al., 2017; Saadi et al., 2022). Moreover, ncRNAs offer promising avenues for the development of novel therapeutic strategies. Targeting ncRNAs with small molecules, antisense oligonucleotides, or RNA-based therapeutics could provide a means to modulate their activity and restore normal gene expression patterns (Forrest and Khalil, 2017; Slack and
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